The goal of this project is to study the role of central oxytocin pathways in the mediation of social attachment. This project uses molecular, cellular, and behavioral techniques with a focus on monogamous mammals. The major finding is that the oxytocin receptor appears to be distributed in markedly different patterns across species, leading to different functional effects of the peptide. In monogamous species, oxytocin receptors are found in pathways implicated in reward. The species differences in receptor distribution are not associated with variations in the coding sequence of the receptor gene but may be due to extensive variation in the promoter. Recently, anatomic and molecular studies in monkeys have been undertaken prior to investigating the human brain. A related receptor, the V1a receptor, has been found in select regions of the rhesus forebrain with binding and in situ hybridization and, based on its pattern of expression, may have an important rol e in memor y. The ultimate purpose of this research is to identify the neural circuitry for attachment behavior, providing a potential map of areas for study in human disorders of social attachment, such as autism. FUNDING NIH / RO1MH56538-02 $149,619 1/01/97 - 12/31/01 PUBLICATIONS Insel, T.R. Towards a neurobiology of attachment. Review of General Psychology (In press). Insel, T.R., O'Brien, D.J. and Leckman, J.F. Oxytocin, vasopressin, and autism. Is there a connection? Biological Psychiatry (In press). Insel, T.R. and Winslow, J.T. Serotonin and neuropeptides in affiliative behaviors. Biological Psychiatry 44:207-219, 1998. Insel, T.R. and Winslow, J.T. The neurobiology of social attachment, in Charney D.S., Nestler, E.J., and Bunney, B.S. (Eds.) Neurobiology of Mental Illness, Oxford University Press, New York (In press). Insel, T.R., Winslow, J.T., Wang, Z. and Young, L.J. Oxytocin, vasopressin, and the neuroendocrine basis of pair bond formation, in Zingg, H.H., Bourque, C.W., and Bichet, D.G. (Eds.) Vasopressin and Oxytocin Molecular, Cellular, and Clinical Advances, Plenum Press, New York, pp. 215-224, 1998. Sanchez, M., Young, L.J., Plotsky, P. and Insel, T.R. Autoradiographic and in situ hybridization localization of corticotropin-releasing factor 1 and 2 receptors in nonhuman primate brain. J. Comp. Neurol. (In press). Wang, Z., Young, L.J., De Vries, G. J. and Insel, T.R. Voles and vasopressin A review of molecular, cellular, and behavioral studies of pair bonding and paternal behaviors, in Urban, I.J.A., Burback, J.P.H., and De Wied, D. (Eds.) Brain Vasopressin and Related Peptides, Signpost (In press). Young, L.J., Toloczko, D. and Insel, T.R. Localization of V1a receptor binding and mRNA in the rhesus monkey brain. J. Neuroendo. (In press). Young, L.J., Wang, Z. and Insel, T.R. Neuroendocrine bases of monogamy. Trends in Neuroscience 21(2):71-75, 1998. P51RR00165-38 1/1/98 - 12/31/98 Yerkes Regional Primate Research Center